1. Oxidative stress and corticoresistance.
Oxidative stress and corticoresistance. Stimulation of alveolar macrophages by pro-inflammatory stimuli activates nuclear factor (NF)-κB and other transcription factors to switch on histone acetyltransferase, leading to histone acetylation and, subsequently, transcription of genes encoding pro-inflammatory chemokines. Corticosteroids reverse this by binding to glucocorticoid receptors and recruiting histone deacetylase (HDAC)2. In chronic obstructive pulmonary disease patients, cigarette smoke generates oxidative stress (acting through the formation of peroxynitrite). This impairs the activity of HDAC2. Consequently, the inflammatory response to NF-κB activation is amplified, and the anti-inflammatory effect of corticosteroids is reduced. ROS: reactive oxygen species. Modified from [17] with permission from the publisher.
N. Roche et al. Eur Respir Rev 2011;20:
©2011 by European Respiratory Society